Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation and is characterized by simultaneous destruction and healing of the tissue from the inflammatory process. Chronic inflammation can also lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer. The autoimmune disorders are different of types disorders of the immune system caused by overactive immune responses. The immune system fails to properly distinguish between self and non-self, and attacks part of the body.
Treatment of rheumatic diseases with gold salts, the so-called gold cure, is an old technique but is still widely used and accepted as a rational treatment of patients who do not respond satisfactorily to the new anti-inflammatory and anti-rheumatic drugs. Like glucocorticoids, injectable gold salts have also shown therapeutic benefits in the treatment of e.g. bronchial asthma. Although the underlying mechanisms have never been fully unraveled, it is known that gold ions alter the function of macrophages by inhibiting their lysosomal enzymes and lowering their production of pro-inflammatory cytokines (Persillin and Schiff 1966; Yanni et al 1994, Nieminen R et al. 2010). Furthermore, gold ions have been shown to inhibit the transcriptionfactor Nuclear Factor-kappaB (NF-kB) (Ligacheva et al. 2012).
It is suggested in U.S. Pat. No. 4,784,991 to use metal salts and in particular gold hyaluronate for the treatment of joint inflammation by administering the salt intra-articularly. In addition, it is disclosed in U.S. Pat. No. 4,746,504 that heavy metal salts of hyaluronic acid, in particular silver, gold, cerium and tungsten salts of hyaluronic acid have also proven to be useful as antimicrobial agents indirectly adding to the effect as an anti-inflammatory reagent. Authorized and scientifically well-founded use of gold in rheumatoid arthritis is mainly performed with various gold-thio compounds such as gold sodium thiomalate such as Myocrisin® available from Aventis Pharma.
Use of gold implants has also been described for the treatment of inflammatory diseases. In WO 02/094294 the metal is implanted or applied locally and provided with a radially enlarged free surface to ensure the greatest possible contact with the affected epithelial tissue. Using autometallography (AMG) it has been shown that from such implants gold ions are liberated in vivo and in vitro (Larsen et al. 2007, Danscher 2002, Danscher and Stoltenberg 2006). The process most likely involves a macrophage-induced reorganization of the biofilm which is created on the metallic surface immediately after an implant is placed in the organism (Larsen et al 2007; see also Sennerby et al 1993; Futami et al 2000; Roach et al 2007). The fact that the released atoms are taken up by cells that trigger the immune response i.e. macrophages and mast cells has initiated intense basic and clinical research projects aimed at revealing whether a sufficient amount of metallic gold can be released from gold implants to implement it in the medical and veterinarian practice as a nontoxic suppressor of local inflammation, i.e. a safe local gold cure.
From e.g. U.S. Pat. No. 7,655,261 it is known to implant distributed metallic gold pieces for example having a diameter of ≥20 μM in a patient to cure or alleviate a plurality of various diseases and conditions. The total surface area of these gold pieces is greater than the surface area of one implanted piece of gold with the same total weight. In U.S. Pat. No. 7,655,261 it is also proposed that the gold pieces be distributed as an open or closed gilding on a support medium for reducing inflammation and stop/suppress release of toxic metal ions from the implant into the body.
The use of gold compounds in medicine has been limited due to adverse effects. Both parenterally and perorally administered gold compounds (i.e. gold salts) can cause pronounced nephrotoxicity because of the intense presence of gold ions in the blood following injection of e.g. Aurothiomalate and careful monitoring is needed when administering the traditional gold compounds (Tozman and Gottlieb 1987; Felson et al 1990). These toxic effects can be by-passed by using local application of metallic gold implants and micro implants i.e. gold particles.
Therefore, it is an object of the present invention to provide a kit, a medical device and methods for improved treatment of immune disorders and cosmetic treatment using gold. It is also an object to provide means and methods for upholding long termed osseointegration.